A Study in Healthy Female Participants to Investigate the Effect of JNJ-56136379 at Steady-state on the Single-dose Pharmacokinetics of Ethinylestradiol and Drospirenone (Oral Contraceptive) and on the Single-dose Pharmacokinetics of Midazolam (Probe Substrate for Cytochrome P450 3A4)

Healthy Clinical Trial

Official title:

A Phase 1, Open-label Study in Healthy Female Subjects to Investigate the Effect of JNJ-56136379 at Steady-state on the Single-dose Pharmacokinetics of Ethinylestradiol and Drospirenone (Oral Contraceptive) and on the Single-dose Pharmacokinetics of Midazolam (Probe Substrate for Cytochrome P450 3A4)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03111511
• Other study ID #: CR108309
• Secondary ID: 56136379HPB10042
• Status: Completed
• Phase: Phase 1
• First received: March 20, 2017
• Last updated: September 1, 2017
• Start date: March 27, 2017
• Est. completion date: August 23, 2017

Study information

• Verified date: September 2017
• Source: Janssen Sciences Ireland UC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to evaluate the effect of steady-state concentrations of JNJ-56136379 on the single-dose pharmacokinetics (PK) of drospirenone and ethinylestradiol (oral contraceptive [OC]) in healthy female participants and to evaluate the effect of steady-state concentrations of JNJ-56136379 on the single-dose PK of midazolam (sensitive probe substrate for CYP3A4) in healthy female participants.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: August 23, 2017
• Est. primary completion date: August 23, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Healthy on the basis of physical examination, medical history, and vital signs performed at screening. If there are abnormalities, the participant may be included only if the investigator judges the abnormalities to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the participant's source documents and initialed by the investigator

• healthy on the basis of clinical laboratory tests performed at screening

• must have a normal 12-lead electrocardiogram (ECG) at screening including: normal sinus rhythm (heart rate between 45 and 100 beats per minute [bpm], extremes included); QT interval corrected for heart rate (QTc) according to Fridericia (QTcF) less than equal to (<=)470 milliseconds (ms); QRS interval less than (<)120 ms; PR interval <=220 ms

• must have a blood pressure (after the participant is supine for 5 minutes) between 90 and 140 millimeters of mercury (mmHg) systolic, inclusive, and no higher than 90 mmHg diastolic. If blood pressure is out of range, up to 2 repeated assessments are permitted

• must have a body mass index (BMI; weight in kg divided by the square of height in meters) between 18.0 and 30.0 kilogram per square meter (kg/m^2), extremes included, and a body weight not less than 50.0 kilogram (kg)

Exclusion Criteria:

• any evidence of heart block or bundle branch block

• history of liver or renal dysfunction (estimated creatinine clearance <60 milliliters per minute (mL/min) at screening, calculated by the Modification of Diet in Renal Disease [MDRD] formula12), significant cardiac, vascular, pulmonary, gastrointestinal (such as significant diarrhea, gastric stasis, or constipation that in the investigator's opinion could influence drug absorption or bioavailability), endocrine, neurologic, hematologic, rheumatologic, psychiatric, neoplastic, or metabolic disturbances

• past history of cardiac arrhythmias (example [eg], extrasystoli, tachycardia at rest), history of risk factors for Torsade de Pointes syndrome (eg, hypokalemia, family history of long QT Syndrome)

• current human immunodeficiency virus type 1 (HIV-1) or HIV-2 infection (confirmed by antibodies) at screening

• any history of clinically significant skin disease such as, but not limited to, dermatitis, eczema, drug rash, psoriasis, food allergy, and urticaria

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Drospirenone/Ethinylestradiol
A single dose of drospirenone/ethinylestradiol 3 mg/0.02 mg (OC) tablets on Days 1 and 21.
• Midazolam
Midazolam 2 mg orally on Days 1 and 21.
• JNJ-56136379
JNJ-56136379 dose will be administered orally at a dose of 250 mg (as 2 tablets of 100 mg + 2 tablets of 25 mg) on Days 6 and 7 and at a dose of 170 mg (as 1 tablet of 100 mg+ 2 tablets of 25 mg + 4 tablets of 5 mg) on Days 8 to 25.

Locations

Country	Name	City	State
Belgium	Clinical Pharmacology Unit	Merksem

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Sciences Ireland UC

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Plasma Concentration of Drospirenone (Cmax)	The Cmax is the maximum observed plasma analyte concentration.	Day 1 and 21: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12 hours postdose
Primary	Area Under the Analyte Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration of Drospirenone (AUC [0-last])	The AUC (0-last) is the area under the analyte concentration-time curve from time 0 to time of the last quantifiable concentration.	Day 1 and 21: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12 hours postdose
Primary	Area Under the Analyte Concentration-time Curve From Time Zero to Infinite Time of Drospirenone (AUC [0-infinity])	The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.	Day 1 and 21: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12 hours postdose
Primary	Maximum Observed Plasma Concentration of Ethinylestradiol (Cmax)	The Cmax is the maximum observed plasma analyte concentration.	Day 1 and 21: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12 hours postdose
Primary	Area Under the Analyte Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration of Ethinylestradiol (AUC [0-last])	The AUC (0-last) is the area under the analyte concentration-time curve from time 0 to time of the last quantifiable concentration.	Day 1 and 21: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12 hours postdose
Primary	Area Under the Analyte Concentration-time Curve From Time Zero to Infinite Time of Ethinylestradiol (AUC [0-infinity])	The AUC (0-infinity) is the area under the analyte concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the analyte concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.	Day 1 and 21: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12 hours postdose
Primary	Maximum Observed Plasma Concentration of Midazolam and its Metabolite 1-OH-Midazolam (Cmax)	The Cmax is the maximum observed plasma analyte concentration.	Day 1 and 21: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 9, 12 hours postdose on Day 1
Primary	Area Under the Analyte Concentration-time Curve From Time Zero to Infinite Time of Midazolam and its Metabolite 1-OH-Midazolam (AUC [0-infinity])	The AUC (0-infinity) is the area under the analyte concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the analyte concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.	Day 1 and 21: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 9, 12 hours postdose
Primary	Area Under the Analyte Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration of Midazolam and its Metabolite 1-OH-Midazolam (AUC [0-last])	The AUC (0-last) is the area under the analyte concentration-time curve from time 0 to time of the last quantifiable concentration.	Day 1 and 21: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 9, 12 hours postdose
Secondary	Number of Participants With Adverse Events as a Measure of Safety and Tolerability	An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	Up to 30-35 days after last study drug administration (approximately 70 days)
Secondary	Maximum Observed Plasma Concentration of JNJ-56136379 (Cmax)	The Cmax is the maximum observed plasma analyte concentration.	1, 2, 4, 9 and 12 hours postdose on Day 21
Secondary	Area Under the Concentration-time Curve From Time Zero to tau Hours Postdose of JNJ-56136379 (AUCtau)	AUCtau is area under concentration-time curve from time 0 to tau hours postdose, calculated by linear-linear trapezoidal summation.	Predose, 1, 2, 4, 9 and 12 hours postdose on Day 21; predose on Day 22
Secondary	Steady-state Plasma Concentration of JNJ-56136379 After Multiple Dosing	Steady-state plasma concentration of JNJ-56136379 will be evaluated after multiple dosing.	Days 16, 19, 20 and 21 (predose)